Gastroretentive Drug Delivery System Research Articles

Preparation and Evaluation of anti-viral drug Zanamivir using different polymers

The dosage forms that stay in the stomach for longer period of time are much more effective to treat any disease. Thus, most approachable and feasible way is to prolong the drug delivery and controlling gastric residence time (GRT) and such kind of dosage forms are known as gastro retentive dosage forms (GRDF). The present study is focused to develop GRDF of Zanamivir. About four formulations of Zanamivir tablets were prepared with different ratios of drug and polymers. The prepared tablets were further evaluated on the basis of precompression and post-compression parameters. The dissolution study of the formulations revealed that formulation F3 using polymer (guar gum) showed 93.4% of in vitro drug release for 8 hours and is the optimized formulation. It was thus concluded that guar gum complies all the properties of floating tablets. Keywords: Zanamivir, Dissolution, Gastro retentive drug delivery system, First pass elimination, Influenza, Prophylaxis

Microballoons: An Advanced Avenue for Gastro Retentive Drug Delivery System

The motivation of writing this review on micro balloons is a Gastro retentive drug delivery system are micro balloons (hollow microsphere) are a drug delivery system that promises to be a potential approach for gastric retention. Microballoons drug delivery system is novel drug delivery on the foundation of non- effervescent system that containing empty particles of spherical shape without core ideally having a size less than 200 micrometers which is designed to be retained in the stomach for a prolonged period of time and release their active ingredients and thereby enable sustained and prolonged input of the drug in the upper part of the gastrointestinal (GI) tract. They are gastro retentive drug-delivery systems, which provide controlled release properties for a drug. Recently gastro retentive drug delivery system (GRDDS) are gaining wide acceptance for drugs with narrow absorption windows, decreased stability at high alkaline pH, and increased solubility at low pH. The design of this article is to compose the various gastro retentive arrive. In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling retention i.e. high density, floating, bio-or that adheres to a mucous membrane (adjective), extensile, attractor etc. In addition of central element controlling gastro retention, superiority and finally future potential are discussed.

A review on Advanced approaches and polymers used in gastroretentive drug delivery systems

Insufficient pharmacokinetic characteristics may be associated with the widespread use of oral dosage forms in the treatment of disease. In some cases, the drug is barely soluble; in others, the formulation's rapid transit through the gastrointestinal tract (GIT) makes it difficult to achieve therapeutic levels in body; in addition, some drugs must act locally due to a gastric pathology, but they remain in the stomach for only a short time. Numerous studies have focused on the development of formulations that are capable of enhancing all of these characteristics and extending the stomach residence duration. The prolonged stomach retention duration afforded by gastroretentive controlled drug delivery devices increases the therapeutic efficacy of many orally administered drugs. In the present investigation, we reviewed the advanced methods and polymers used to develop effective gastroretentive drug delivery systems. These methods include swelling and expansion, mucoadhesive, high density, low density, ion exchange, raft forming, magnetic, and floating drug delivery systems. The development of gastroretentive devices involves a broad array of polymeric materials. This work intends to expedite the development of innovative methods by offering a comprehensive understanding of unique gastroretentive approaches along with the polymeric materials utilised in the fabrication of gastroretentive drug delivery systems for oral drug delivery.
 Keywords: Gastroretentive; mucoadhesive; floating; raft forming system; mucoadhesive; swellable.

Formulation Development and Evaluation of Floating Tablets of Zolmitriptan

Zolmitriptan is the antimigraine agent widely used for the treatment of the migraine. It shows the half-life of 2.5 – 3 h which indicate the frequent dosing to achieve proper pharmacological action of the drug. Gastro Retentive Drug Delivery System (GRDDS) is a common approach to decrease the dosing frequency and increase patient compliance, and delivery of drug through such an approach of floating tablet formulation will meet the requirement. This system showed substantial effect on the drug release through floating and swelling properties. The tablets were formulated by using direct compression technique along with hydrophilic polymers and gas generating system. In the preliminary trials, we observed that the tablets were within pharmacopeial limit. % Drug release of the formulations (F1 – F9) was studied up to 6 h and it was found from 52 to 91 %. The cumulative percentage drug release was inversely proportional to polymer concentrations of HPMC K100 M and PVP K 30. The batches follow Higuchi model of drug release which involves the diffusion mechanism. In-vitro dissolution studies showed good percent drug release, which is in accordance with robinson-errikson equation. Good buoyancy for additional 6 h, trailed by the diffusion.

Different evaluation parameters of floating microsphere of ofloxacin

The Floating Microsphere of Ofloxacin requires a novel gastroretentive drug delivery system which can provide an extended period of time in stomach and improve oral bioavailability. Floating microspheres were characterized for floating ability, compatibility study, particle size and shape, entrapment efficiency, in-vitro drug release. Due to their low density, these multi particulate drug delivery systems showed good floating ability and remained in gastric environment for more than 24 hrs, required for sustained therapeutic activity. Major advantages of the system include ease of preparation, good floating ability, high encapsulation efficiency and sustained drug release over 24 hours. From this study, it was concluded that formulation of floating microspheres of ofloxacin offers prolonged gastric residence time and continuous release of the medication over an extended period of time thus oral bioavailability of the drug and subsequent efficacy is improved.

DEVELOPMENT AND CHARACTERIZATION OF SUSTAINED RELEASE GASTRO-RETENTIVE FLOATING TABLETS OF AMBROXOL HYDROCHLORIDE

Introduction: The objective of this study was to formulate floating tablets of Ambroxyl hydrochloride (AMB HCl) using the dry granulation technique to increase its bioavailability and the gastric residence time (GRT) of the dosage form. Materials and Methods: The gastro-retentive floating tablets of Ambroxol hydrochloride (AMB HCl) were prepared by direct compression method using different concentrations of polymers such as HPMC K4, HPMC K15 and PVP K30, gas releasing agents (Sodium bicarbonate and citric acid) and diluents (Microcrystalline cellulose). Citric acid was also used as an antioxidant. The final mixing was done by adding talc and magnesium stearate to the granules. Results and Discussion: The prepared formulation of AMB HCl was evaluated by some evaluation parameters such as hardness, friability, weight variation, buoyancy lag time, drug contents, total floating time, in vitro dissolution study, drug release study etc. The result from the FT-IR data study of formulation it was disclosed that there is no interaction between the drug and excipients. In the FT-IR study, it was revealed that there is no interaction between the drug and excipients. The formulation containing the combination of HPMC K 15M polymer and Sodium bicarbonate shows a good drug release pattern with less floating lag time and good floating duration. In vitro drug release study of the prepared formulation (gastro retentive floating tablets of AMB HCl) was shown that the formulation F5 was the best formulation which was found to be 99.87% drug release. The release mechanism and its kinetics were evaluated by plotting various mathematical models of release data such as the Higuchi model, Korsmeyer model, First order and Zero order drug release. The optimized formulation showed no significant change at various evaluation parameters such as hardness, friability, weight variation and % drug release for accelerated stability condition at 40±2oC temperature and 75±5% (RH) relative humidity for 3 months. The floating tablets of AMB HCl showed their potential over a prolonged period as a gastro retentive drug delivery system (GRDDS).

Scope and Limitations of Current Antibiotic Therapies against Helicobacter pylori: Reviewing Amoxicillin Gastroretentive Formulations.

Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are linked to an infection of Helicobacter pylori; in fact, this pathogen has already been categorized as a group 1 carcinogen by the World Health Organization (WHO). Still, the efficacy of current anti-H. pylori therapeutic approaches is insufficient and follows a worrying decreasing trend, mainly due to an exponential increase in resistance to key antibiotics. This work analyzes the clinical and biological characteristics of this pathogen, especially its link to gastric cancer, and provides a comprehensive review of current formulation trends for H. pylori eradication. Research effort has focused both on the discovery of new combinations of chemicals that function as optimized antibiotic regimens, and on the preparation of gastroretentive drug delivery systems (GRDDSs) to improve overall pharmacokinetics. Regarding the last topic, this review aims to summarize the latest trend in amoxicillin-loaded GRDDS, since this is the antibiotic that has shown the least bacterial resistance worldwide. It is expected that the current work could provide some insight into the importance of innovative options to combat this microorganism. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of this infection and the consequent prevention of gastric cancer.

Gastroretentive Sustained-Release Tablets Combined with a Solid Self-Micro-Emulsifying Drug Delivery System Adsorbed onto Fujicalin®.

Gastroretentive drug delivery systems (GRDDS) get retained in the stomach for a long time, thus facilitating the absorption of drugs in the upper gastrointestinal tract. However, drugs that are difficult to dissolve or unstable in an acidic environment are not suitable for GRDDS. The current study designs GRDDS combined with a self-micro-emulsifying drug delivery system (SMEDDS) for drugs with solubility or stability problems in the stomach. The model drug fenofibrate was formulated into the optimized liquid SMEDDS composed of 50 w/w% Capryol® PGMC, 40 w/w% Kolliphor® RH40, and 10 w/w% Transcutol® HP and solidified through adsorption on several porous adsorbents. In a dissolution medium at pH 1.2, the powdered SMEDDS using Fujicalin® dissolved quickly and achieved higher drug dissolution than other adsorbents. Based on these results, a gastroretentive bilayer tablet consisting of a drug release layer and a swelling layer was designed. The drug release layer was formulated with the powdered SMEDDS and hydroxypropyl methylcellulose (HPMC) as a release modifier. HPMC was also added to the swelling layer as a water-swellable polymer. The dissolution rate depended on the viscosity of the HPMC in the drug release layer. The time for 90% drug release was extended from 3.7 to 12.0h by increasing the viscosity grade of HPMC from 0.1 to 100K. Moreover, the tablet swelled and maintained a size comparable to a human pylorus diameter or more for at least 24h. This GRDDS could apply to a broader range of drug candidates.

Fabrication and Applications of Raft-Forming System - An Emerging Trend in Gastro-retentive Drug Delivery System

Background and Objective: In the past several decades, the gasto-retentive drug delivery system is considered as a novel approach and has gained immense popularity in the field of novel drug delivery systems. Among several approaches to achieve gastric retention raft forming system which comes under the classification of floating drug delivery system is a subject of special research interest. This advanced drug delivery system has the potential to attain a prolonged and predictable drug delivery at specific sites of the GI tract mainly in the stomach and intestine thereby exhibiting a relatively constant plasma profile. Thus, the floating raft forming system finds useful over conventional therapeutics to treat several gastrointestinal disorders viz., gastro esophageal reflux disorder, acid reflux, peptic ulcer, oesophagitis, etc. Methods: In this current manuscript, an extensive search is performed for original research papers using databases viz., Google Scholar, PubMed, Science Direct, etc. Further, painstaking efforts are made to compile and update the recent findings of the formulation scientists working exclusively in the area of raft forming systems. This article portrays a detailed survey about several applications of raft forming systems in the form of tables. Conclusion: The floating raft forming system has the potential for controlled drug release in the upper part of the GI tract and exerts improved bioavailability of the medications having a narrow absorption window. Thus, it is concluded that this advanced dosage form is the caliber candidate for the treatment of several gastrointestinal ailments.

Recent Advance in Gastroretantive Drug Delivery System (GRDDS)

The drug delivery system is most important and preferable drug delivery system. This route has high patient acceptability, primarily due to easy of administration. Effective oral drug delivery depends upon the factors such as gastric emptying process, the gastrointestinal transit time of the dosage form drug release from the dosage form, and site of absorption of drug. In recent years, scientific and technological advancements have been made in the research and development of gastro retentive drug delivery systems. Hence forth a wide spectrum of dosage forms has been developed for the drugs which have narrow absorption window, unstable at intestinal pH, are soluble in acidic pH, and have a site of action specific to stomach. The purpose of writing this review was to investigate, compile and present the recent as well as past literature in a more concise way with a special focus on approaches that are currently utilized in the prolongation of gastric residence time. These include floating system, swelling and expanding system, bio/mucoadhesive system, high-density system, and other delayed gastric emptying devices. The present review addresses briefly the classification, formulation consideration for Gastroretantive drug delivery system (GRDDS), factors controlling gastric retention, merits, demerits, and applications of gastro retentive drug delivery systems.

Formulation and Evaluation of Superporus Hydrogel Composite as a Gastro Retentive Drug Delivery for Cefditoren Pivoxil

The purpose of this work was to incorporate superporus hydrogels for cefditoren pivoxil by using polymer like poly acrylic acid aqua cc polymer and composite agent like cross linked sodium carboxy methyl cellulose in the presence of N,N-methylene-bis-Acrylamide as crosslinking agent. Pluronic F-127 as a stabilizer and ammonium per sulfate and tetramethylene diamine as a initiator pair. Poly acrylic acid aqua cc polymer-cross linked sodium carboxy methyl cellulose superporus hydrogels of cefditoren pivoxil were incorporate by gas blowing technique. The reaction of pH on the swelling ratio was decisive. Swelling reversibility research was also achieve. Fourier transform infrared spectroscopy analysis and scanning electron microscopy studies were assume to indicate the drug loaded superporous hydrogels, while dissolution studies were achieve to assess release characteristics. Swelling was hugely depending on the term of crosslinking and the quantity of the polymer existing in formulation. The huge amount of cross-linking agent reduced the swelling ratio. The superporous hydrogels were hugely perceptive to pH of swelling medium, and exhibit reversible swelling and de-swelling behavior during still keep their mechanical stability. Apparent density was reliant on the amount of the superporous hydrogels and reduced with developing crosslink density. Degradation kinetics reveals that poly acrylic acid aqua cc polymer superporous hydrogels had good water holding potential. Drug release was similar to quantity of cross-linking agent. The studies report that poly acrylic acid aqua cc polymer superporous hydrogels can be used as a Gastroretentive drug delivery system in view of their swelling characteristics in acidic pH.

In-vivo study of quetiapine fumarate superporous hydrogels

This study aims to design and evaluate a gastroretentive drug delivery system using second generation Superporous hydrogels using Factorial design approach. Optimized formulation was assessed for pharmacokinetic parameters by In-vivo study. Pharmacokinetic analysis of Quetiapine Fumarate plasma concentration–time data provided the following pharmacokinetic parameters like Cmax values ranging (690.58 ± 1.1 ng/mL to 524.37 ± 1.6 ng/mL), Tmax values ranging (1.5 ± 0.0 to 6.0 ± 0.0 Hours), AUC values ranging (5345.67 ± 11.34 h.ng/mL to 5345.67 ± 4.59 h.ng/mL). Results obtained for the formulated product prepared with superporous hydrogel technology shows prolonged release while maintaining Q Value with reduce plasma drug fluctuations in comparison to the Pure drug.

COMPREHENSIVE OVERVIEW ON RECENT UPDATES OF GASTRORETENTIVE RAFT-FORMING SYSTEMS

A Raft-forming system is an auspicious approach for systematic drug delivery with steady plasma profiles and drug sustained release manner. It has advantages like enhanced bioavailability, better floating capabilities than other floating systems, more patient compliance, and promoting drug efficacy. Although, it has some problems as it can’t be used for drugs that possess low acid solubility, drugs that are unstable in gastric media, and drugs used for selective release in the colon along with stability difficulties. This system can be successfully prepared by three methods: the physical approach, chemical approach, and physiologically-stimuli approach. The comparative studies showed that the raft-forming system has more advantage over the other comparatives in the antacid potency and in vitro gastric residence time, allowing an intact prolonged delivery of the antacid drug. All the listed applications of the raft system were, fortunately, possessing promising drug delivery with a well-designed drug delivery system. There was a good variety in the active ingredients formulated in a raft, starting from some anti-coughs, anti-spasmodic, anti-inflammatories, and antacids to drugs treating osteoporosis and finally anti-depressants and anti-epileptic drugs. This diversity along with simple in vitro and in vivo evaluations, gives the potentiality to raft for leading the other gastro retentive drug delivery systems for decades.

The Development of Gastro-Retentive Tablet using Hot Melt Extrusion and 3D Printing Technology

In this study, a three-dimensional (3D) printed gastro-retentive tablet (3DPGRT) containing sarpogrelate HCl was prepared by changing the amount of the polymers (Eudagit？？L100-55 (EuL), pectin, and polyethylene oxide (PEO)) by coupling hot melt extrusion (HME) and 3D printing technology. The study aims to evaluate the swelling and dissolution behavior for application as a gastro-retentive drug delivery system and optimize the formulation of 3DPGRT based on the design of experiment using central composite design. The flexibility and elasticity of the extruded filaments were affected by EuL, pectin, and PEO, which either showed a linear or quadratic pattern. 3DPGRT containing sarpogrelate HCl was fabricated successfully by coupling HME and a fused deposition modeling 3D printer without being affected by EuL, pectin, and PEO. Compatibility studies of the drug-excipient through FT-IR and DSC revealed the absence of any interaction between the drug and polymers. The developed 3DPGRT possessed the ability to float over 10 h. The dissolution rate of sarpogrelate HCl was significantly affected by the interaction between EuL and pectin. The results confirmed that the mechanism of drug release of 3DPGRT is caused by a combination of non-Fickian diffusion and dilatation, which fits well with the Higuchi and Korsmeyer-Peppas model. The optimized formulation have been obtained by numerical optimization, which yielded excellent floating properties and a desirable swelling ratio with controlled drug release. This study showed the application of quality by design in the formulation development of 3DPGRT coupled with HME, which can be used to control the swelling characteristics and dissolution behavior through the interaction between EuL and pectin.

HPMC Based Gastro Retentive Drug Delivery System of Effervescent Guifenesine Tablet for Dry Cough

Recent advances in Novel Drug Delivery System is aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. The controlled release drug delivery systems owning the capacity to be engaged in the stomach remains entitled as Gastro Retentive Drug Delivery Systems. One of the novel approaches for better patient compliance is floating drug delivery. Number of Gastro Retentive dosage forms has been designed to prolong gastric residence time. We are trying to overcome less gastric retention time and trying to reduce the dosing frequency. Gastroretentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Present study involves preparation of floating tablet of Guaifenesin with HPMC K10 and K15M floating tablet were designed to achieve the extended release or retention in GIT, which may result enhance in absorption and leads to increase in bioavaibility. The aim of the present work is to develop safe, effective HPMC based gastro retentive drug delivery system of effervescent Guaifenesin tablet for dry cough with extended release profile.

Flaxseed Mucilage Hydrogel based Floating Drug Delivery System: Design and Evaluation

Natural polymer-based plant polysaccharides and proteins have been most widely explored as an adjuvant in the dosage form formulation. Here we design a novel gastro-retentive floating tablet, based on a polysaccharide material from Flaxseed (Linum usitatissimum L.) for Domperidone. After oral administration; Domperidone showed good solubility in acidic pH but significantly reduced solubility in alkaline medium. So that to increase the absorption and bioavailability of Domperidone, it is necessary to increase the retention time in the upper part of the Gastrointestinal tract (GIT) by developing a floating sustained drug delivery system. The directly compressible floating tablets of domperidone were formulated using varying amount of hydroxypropyl methylcellulose K 100 M (HPMC K100 M), Carbopol 934 and Flaxseed mucilage. Hardness, friability, weight variation, thickness, disintegration time of tablet formulations were within acceptable limits. The overall results explained that the optimized formulation F5 prepared by the exact ratio of Flaxseed mucilage, HPMC K100 M, Carbopol, could be more efficient on floating and sustained release of Domperidone in the upper part of GIT as compared to the tablets prepared by using HPMC K100 M and Carbopol 934 only. These findings indicated that Flaxseed can be used to develop novel gastro-retentive sustained release drug delivery system with the double advantage of sustained drug release at the upper part of GIT.

Formulation and evaluation of gastro retentive drug delivery system of candesartan cilexetil

It had became a challenging experience and effort for a formulator to develop and innovate a drug with maximum bioavailability. In the present study the focus of research is in the treatment of Hypertension, which is one of the most prevalent cardiovascular diseases in the world, affecting a big proportion of the adult and old age population. Candesartan Cilexetil angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands, used for the treatment of high blood pressure. The drug has poor bioavailability due to limited oral absorption and maximum absorption at proximal intestine. This warrants and offers the use of Gastro Retentive Drug Delivery System (GRDDS) for sustained release formulation in order to achieve prolonged action and to improve patients compliance. Wet granulation technique was selected for preparation of tablets and the drug is formulated with HPMC K100M, ethylcellulose, sodium bicarbonate, Micro crystalline cellulose, Gelucire, talc and Aerosil etc. For around twelve formulations were made and evaluated for General appearance, Thickness, Hardness or Crushing strength Test, Friability Test, Estimation of drug content, In-vitro buoyancy studies and In-vitro drug release and the results obtained for the performed tests were found with in the range specified limits.

Novel approaches of gastro retentive drug delivery system

Oral route of drug administration is the most convenient route and accepted route of drug delivery. It is probable that at least 90% of all the drugs given by oral route. There are different drug deliveries to cure the diseases through oral route. Among them Gastroretentive drug delivery system plays an important and significant role in novel drug delivery systems. The floating systems, bioadhesive drug delivery system, expandable drug delivery system, high density systems, effervescent systems (Gas Generating systems), non-effervescent systems etc are various approaches. The wide applications can be achieved through this delivery system are enhanced bioavailability, sustained drug delivery, site-specific drug delivery, absorption enhancement, mitigating adversity at colon etc. In addition to specified above, the advantages and disadvantages, drugs and polymers used and the method of evaluation is also summarized in this review.

Formulation and evaluation of gastroretentive drug delivery system of eprosartanmesylate

It had became a challenging experience and effort for a formulator to develop and innovate a drug with maximum bioavailability. Objective: In the present study the focus of research is in the treatment of Hypertension, which is one of the most prevalent cardiovascular diseases in the world, affecting a big proportion of the adult and old age population. Eprosartan mesylate(EPM) is angiotensin-II receptor antagonist used for the treatment of high blood pressure. The drug has poor bioavailability due to limited oral absorption and maximum absorption at proximal intestine. This warrants and offers the use of Gastro Retentive Drug Delivery System (GRDDS) for sustained release formulation in order to achieve prolonged action and to improve patients compliance. Method: Wet granulation technique was selected for preparation of tablets and the drug is formulated with hydroxyl propyl methyl cellulose K100m, hydroxyl propyl methyl cellulose K15m, polyox WSR coagulant, polyox WSR301,polyox WSR N80, Lactose Monohydrate, Micro crystalline cellulose(Avicel), magnesium sterate, ethylcellulose, sodium bicarbonate, tromethamine, etc. Results: For around twenty formulations were made and evaluated for General appearance, Thickness, Hardness or Crushing strength Test, Friability Test, Estimation of drug content.

Design and Evaluation of Gastro-retentive Drug Delivery System for Glimepiride using Design of Experiment

Glimepiride, oral sulfonyl urea, BCS class-II drug is used to treat diabetes (type-II). Due to its low solubility, it is an ideal candidate for solubility enhancement, leading to better bioavailability and subsequent dose. In the present study, the solid dispersion technique was used to improve the solubility using solvent evaporation method. The solid dispersions were prepared using affnisol 912 as a solubility enhancer. The prepared solid dispersions were evaluated for solubility in 0.1N HCl pH 1.2 and phosphate buffer pH 7.8 medium. The solubility of glimepiride in optimized solid dispersion (SD1) formulation was 682.44 µg/mL compared to 6.88 µg/mL for pure drug in pH 7.8 medium. The solid dispersion (SD1) was further formulated into the tablets. The gastro-retentive and mucoadhesive properties were contributed to the tablets by HPMC K4M and Carbopol 940, respectively. Factorial design (Central composite design) was used to optimize the gastro-retentive tablets. The tablet formulations showed good mucoadhesive properties and drug release up to 12 hours in pH 1.2 with 0.5% SLS medium. The optimized formulation (F2) showed cumulative drug release up to 97.20 ± 0.99% in 12 hours. The drug release kinetics also showed that the drug is release by dissolution and diffusion from the drug matrix. The gastro-retention studies in rabbits also showed the tablets remain within the GIT up to 12 hours as confirmed by x-ray images.